Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Onchocerca volvulus superoxide dismutase was expressed in Escherichia coli, using a protocol designed to produce the native enzyme rather than a fusion protein. The recombinant O. volvulus superoxide dismutase (rOVSOD) was found in the cytosol of the disrupted bacteria and represented > 10% of the total bacterial protein. The enzyme was purified to homogeneity using DEAE-Sepharose chromatography, followed by phenyl-Sepharose chromatography. The rOVSOD was enzymatically active which was demonstrated by its reactivity with O2.- produced either by the xanthine-xanthine oxidase system or by stimulated eosinophils. The specific activity was determined to be 4668 U mg-1. This activity could be blocked by rabbit antiserum raised against the rOVSOD. The maximal activity was obtained upon supplementation of the bacterial growth media and enzyme buffer with copper and zinc ions. Activity characteristics in the presence of inhibitors was also characteristic of a Cu/Zn superoxide dismutase. The rOVSOD has an apparent subunit molecular mass of 16,000 in SDS-PAGE. The active enzyme behaves as a dimer of 32 kDa as determined by gel filtration.
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PMID:Characterization of enzymatically active Onchocerca volvulus Cu/Zn superoxide dismutase expressed in Escherichia coli. 783 82

The reactivity and toxicity of nitric oxide is modest in comparison to oxidants derived from nitric oxide. Exposure of Escherichia coli to 1 mM nitric oxide under aerobic or anaerobic conditions did not decrease viability of the bacteria. Peroxynitrite (1 mM), the reaction product of superoxide and nitric oxide, was completely bactericidal after 5 s. The nitrovasodilator, 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1), slowly decomposes to release both nitric oxide and superoxide and thereby produces peroxynitrite. SIN-1 killed E. coli in direct proportion to its concentration with an LD50 of 0.5 mM. Copper, zinc superoxide dismutase (50-400 units/ml) provided substantial but not complete protection against SIN-1 killing. Catalase (500-10,000 units/ml) partially protected in direct proportion to its concentration, while inactivated catalase was not protective. Superoxide dismutase and catalase together completely protected E. coli against SIN-1 toxicity. Oxy-hemoglobin eliminated both SIN-1 and peroxynitrite toxicity. The bactericidal activity of SIN-1 was further enhanced by pterin plus xanthine oxidase. Pterin plus xanthine oxidase alone or together with Fe3+ ethylenediamine tetraacetate produced no significant decrease in E. coli viability. Hydrogen peroxide was not directly toxic to the bacteria, but E. coli pretreated with hydrogen peroxide were more susceptible to peroxynitrite, SIN-1, and the aerobic oxidation products of nitric oxide. Hydrogen peroxide pretreatment did not increase significantly the toxicity of nitric oxide under anaerobic conditions. Our results suggest that peroxynitrite is far more toxic to E. coli than nitric oxide or its by products from aerobic oxidation.
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PMID:The comparative toxicity of nitric oxide and peroxynitrite to Escherichia coli. 784 Jun 33

Effects of Cu2+,Zn2+,Fe2+ and selenium ions on the conversion of xanthine dehydrogenase to oxidase in rabbit liver were examined. Under basal conditions, xanthine oxidase activity represented only 16% of the total xanthine oxidase plus dehydrogenase activity. Cu2+ (2-10 microM), Zn2+ (5-30 microM) and selenium ions (5-100 microM) brought about the conversion of xanthine dehydrogenase to oxidase in a dose-dependent manner. The concentrations of Cu2+,Zn2+ and selenium ions required for increasing xanthine oxidase activity by 50% was approximately 4, 10 and 20 microM, respectively. On the other hand, Fe2+ had no effect on the conversion of the enzyme up to 100 microM. These results suggest that Cu2+,Zn2+ and selenium ions have the potential to modulate the conversion of xanthine dehydrogenase to oxidase in rabbit liver.
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PMID:Induction of the conversion of xanthine dehydrogenase to oxidase in rabbit liver by Cu2+,Zn2+ and selenium ions. 793 44

It was revealed that Zinc deficiency might cause taste and smell dysfunction. Superoxide dismutase (SOD), which scavenges superoxide, is a type of zinc enzyme. It was also demonstrated that the overproduction of superoxide damages normal tissue. We therefore measured the activity of SOD in serum and saliva of patients with taste or smell dysfunction by the cytochrome C reduction method using a xanthine-xanthine oxidase system. As a result, in the patients with taste dysfunction, the activities of SOD in both serum and saliva were normal, but mean level of serum Zinc was near to the lower normal limit. On the other hand, in the patients with smell dysfunction caused by chronic sinusitis or common cold, the activity of SOD in serum was significantly lower than that of healthy volunteers, and that in saliva was normal. These results suggest that Zinc enzymes, except serum and salivary SOD, are involved in the sense of taste, and that further investigation is necessary to clarify the relation between serum SOD deficiency and olfactory dysfunction.
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PMID:[The activity of superoxide dismutase in patients with taste and smell dysfunction]. 796 80

The presence of superoxide dismutase (SOD) activity in the bovine lungworm Dictyocaulus viviparus was examined using the xanthine-xanthine oxidase assay system and by non-denaturing PAGE followed by specific enzyme staining. High levels of activity were detected in excretory-secretory (ES) products of adult worms and in soluble extracts of both the L3 and adult stages of the parasite. Stage-specific and ES-specific activities were indicated by differences in SOD isoenzyme profiles between adult and larval parasite extracts and between adult extract and ES products, with a fast migrating activity being specific to ES products. All isoenzymes were sensitive to cyanide, indicating copper/zinc dependency. The antigenicity of ES SOD was demonstrated by a reduction in SOD activity in both the chemical assay and non-denaturing PAGE following incubation of parasite ES products with IgG antibody purified from serum of infected or vaccinated bovine hosts. The high level of SOD activity released by adult D. viviparus may be a reflection of the problems faced by a parasite occupying an oxygen-rich environment. Antibody inhibition of SOD may, therefore, be an important target of protective immunity.
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PMID:Superoxide dismutase (SOD) activity of Dictyocaulus viviparus and its inhibition by antibody from infected and vaccinated bovine hosts. 808 70

The inhibition of the activity of bovine xanthine oxidase (XO) by divalent mercury and other metal ions has been investigated by optical spectroscopy and stop-flow kinetic measurements. The study shows that Hg2+ ion completely inhibits the activity of XO, while other metal ions such as Zn2+, Mg2+, Co2+, and Ni2+ inhibit the activity only marginally (approximately 10%). The inhibition by the Hg2+ ion was found to be monophasic and noncompetitive with strong affinity for binding to XO. The pH-dependent study of the inhibition indicates that at least two ionizing groups of XO are involved in the binding of the Hg2+ ion.
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PMID:The inhibition of bovine xanthine oxidase activity by Hg2+ and other metal ions. 867 4

Rat hepatocytes were isolated by a two-step collagenase perfusion technique and introduced to the hydroxyl radical (OH)-generating xanthine-xanthine oxidase-iron (X/XO/Fe) system. The amount of thiobarbituric acid reactive substances (TBA) and thiobarbituric acid bound malondialdehyde (TBA-MDA) were assayed in homogenates after different phases of cultivation. The effects on lipid peroxidation of supplemented metallothionein (MT) ranging from 25 to 75 microM and zinc ranging from 14.5 to 77.8 microM, as well as the effect of a Zn-pretreatment for 18 h were investigated. The addition of X/XO/Fe resulted in a 3 to 4-fold increase in the levels of TBA and TBA-MDA. These results show that X/XO/Fe initiated the lipid peroxidation in the hepatocyte cell system. High doses of supplemented MT inhibited the production of TBA and TBA-MDA. Neither Zn nor the Zn-pretreatment, which resulted in an increase of intracellular MT, had any effect on TBA and TBA-MDA levels. This study suggests that MT can act as an antioxidant in high concentrations via the cysteinyl groups of the protein. The postulated protective effects of Zn via its release from the oxidized MT can be ruled out.
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PMID:Metallothionein and zinc as potential antioxidants in radical-induced lipid peroxidation in cultured hepatocytes. 882 31

Based on the inhibition of nitrite formation by generating superoxide from xanthine/xanthine oxidase (X/XO) reaction system, metallothionein (MT) and other sulfhydryl containing amino acids have been selected to test their abilities to scavenge superoxide radicals. Different concentrations of metallothionein and other sulfhydryl containing molecules e.g. cysteine, N-acetyl-cysteine and glutathione, were used to assess superoxide scavenging properties. Metallothionein scavenges superoxide radical in a dose-dependent manner with increasing concentrations as evidenced by the inhibition of nitrite formation. Similar abilities to scavenge superoxide radicals were shown by cysteine, N-acetyl-cysteine. Glutathione also scavenges superoxide radical in a dose-dependent manner. In vitro experiments demonstrated that metallothionein is superior in scavenging superoxide radicals compared to other sulfhydryl molecules such as cysteine, N-acetyl-cysteine and even glutathione. The data, further, suggest that metallothionein-II has a 6-fold higher capacity to scavenge superoxide radical than metallothionein-I. In addition, metallothionein-like protein was isolated from different regions of mouse brain treated with zinc. Brain metallothionein-like protein inhibits nitrite formation as demonstrated by other scavengers; however, the extent of inhibition is different by this protein isolated from different brain regions. The present study suggests that metallothioneins and metallothionein-like proteins isolated from mouse brain act as neuroprotective agents by scavenging superoxide radicals.
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PMID:Role of metallothionein and other antioxidants in scavenging superoxide radicals and their possible role in neuroprotection. 883 43

Aristolochic acid I (AAI) and aristolochic acid II (AAII), the two major components of the carcinogenic plant extract aristolochic acid (AA), are known to be mutagenic and to form DNA adducts in vivo. According to the structures of the major DNA adducts identified in animals and humans, nitroreduction is the crucial pathway in the metabolic activation of these naturally occurring nitroarenes to their ultimate carcinogenic species. Using the nuclease P1-enhanced version of the 32P-post-labelling assay we investigated the formation of DNA adducts by AAI and AAII in different in vitro activation systems in order to determine the most suitable in vitro system mimicking target tissue activation. Although DNA adducts resulting from oxidative activation of AAs have not yet been identified both reductive and oxidative in vitro systems were employed. In vitro incubations were conducted under standardized conditions (0.3 mM AAs; 4 mM dNp as calf thymus DNA) using rat liver microsomes, xanthine oxidase (a mammalian nitroreductase), horseradish peroxidase, lactoperoxidase and chemical reduction by zinc. Enzymatic incubations were performed under aerobic and anaerobic conditions. A combination of two independent chromatographic systems (ion-exchange chromatography and reversed-phase HPLC) with reference compounds was used for the identification of DNA adducts detected by the 32P-post-labelling assay. The two known major adducts of AAI or AAII found in vivo were generated by all in vitro systems except for incubations with AAII and horseradish peroxidase where two unknown adducts predominated. Irrespective of the in vitro activation system used, the majority of adduct spots obtained were identified as the previously characterized four AA-DNA adducts: dA-AAI, dA-AAII, dG-AAI and dG-AAII. This indicates that both reductive and peroxidative activation of AAI or AAII resulted in chromatographically indistinguishable DNA adducts. Thus, peroxidase mediated activation of AAs led to the formation of the same adducts that had been observed in vivo and upon reductive activation in several in vitro systems. Quantitative analyses of individual adducts formed in the various in vitro systems revealed relative adduct labelling (RAL) values over a 100,000-fold range from 4 in 10(3) for activation of AAII to deoxyadenosine adducts by zinc to only 3 in 10(8) for activation of AAII by lactoperoxidase. The extent of DNA modification by AAI was higher than by AAII in all enzymatic in vitro systems. Only activation by zinc resulted in higher total binding to exogenous DNA by AAII than by AAI. Aerobic incubations with rat liver microsomes generated AAI- and AAII-DNA adduct profiles reproducing profiles in target tissue (forestomach) of rats, thus providing the most appropriate activation among the in vitro systems tested.
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PMID:Comparison of DNA adduct formation by aristolochic acids in various in vitro activation systems by 32P-post-labelling: evidence for reductive activation by peroxidases. 916 96

Meningococcal sodC encodes periplasmic copper- and zinc-cofactored superoxide dismutase (Cu,Zn SOD) which catalyzes the conversion of the superoxide radical anion to hydrogen peroxide, preventing a sequence of reactions leading to production of toxic hydroxyl free radicals. From its periplasmic location, Cu,Zn SOD was inferred to acquire its substrate from outside the bacterial cell and was speculated to play a role in preserving meningococci from the action of microbicidal oxygen free radicals produced in the context of host defense. A sodC mutant was constructed by allelic exchange and was used to investigate the role of Cu,Zn SOD in pathogenicity. Wild-type and mutant meningococci grew at comparable rates and survived equally long in aerobic liquid culture. The mutant showed no increased sensitivity to paraquat, which generates superoxide within the cytosol, but was approximately 1,000-fold more sensitive to the toxicity of superoxide generated in solution by the xanthine/xanthine oxidase system. These data support a role for meningococcal Cu,Zn SOD in protection against exogenous superoxide. In experiments to translate this into a role in pathogenicity, wild-type and mutant organisms were used in an intraperitoneal mouse infection model. The sodC mutant was significantly less virulent. We conclude that periplasmic Cu,Zn SOD contributes to the virulence of Neisseria meningitidis, most likely by reducing the effectiveness of toxic oxygen host defenses.
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PMID:Periplasmic superoxide dismutase in meningococcal pathogenicity. 942 60


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